This research proposal is concerned with the role of lymphokines in hypersensitivity granulomatous lung reactions. The main objective is to investigate the role of partially purified chemotactic and migration inhibitory factors in the generation of mononuclear pulmonary granulomas which form around a solid nidus. The research objectives can be divided into four areas: 1. Production of lymphokine-rich supernatants from: a) antigen-stimulated spleens of S. mansoni infected mice, b) antigen-stimulated, artificial hypersensitivity granulomas isolated from the lungs of sensitized, challenged animals, and c) mitogen-stimulated normal spleens. 2. Fractionation and initial purification of the crude, active supernatants by Sephadex columns and isoelectric focusing: examination of the fractions for chemotactic and migration inhibitory activity. Active fractions will be further characterized as to molecular size, heat and enzyme (neuraminidase, chymotrypsin) sensitivity and elicitation of elevated 1-14C glucose oxidation in macrophages. 3. Fluid lymphokines or lymphokines bound covalently to Sepharose beads will be injected into the lungs of normal mice and the ensuing granulomatous response around the solid nidi will be quantitated in stained histologic sections. 4. The effect of fluid or bead-bound lymphokine on: a) the dynamics of thymidine labelled, bone marrow-blood monocyte-alveolar macrophage-granuloma macrophage sequence, b) the granulomatous response of lethally irradiated mice reconstituted with bone marrow cells, peritoneal and alveolar macrophages, and c) the recirculation and homing of chromium labelled peritoneal and alveolar macrophages, will be examined.